Investigating N-3 Fatty Acids to prevent Neonatal Tobacco-related outcomeS (INFANTS)

研究 N-3 脂肪酸以预防新生儿烟草相关后果（婴儿）

基本信息

批准号：
10017308
负责人：
Harvey J. Murff
金额：
$ 72.17万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-13 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10017308
关键词：
Address Adverse effects Area Biochemical Biological Markers Birth Bupropion Carbon Monoxide Cigarette Clinic Clinical Clinical Research Clinical Trials Cotinine Data Discipline of obstetrics Double-Blind Method Effectiveness Enrollment Erythrocytes FDA approved Fatty Acids Fetal Growth Retardation Fish Oils Gestational Age Health Intervention Intervention Studies Knowledge Measures Mediating Mediation Medical Records Membrane Neonatal Nicotine Dependence Omega-3 Fatty Acids Outcome Participant Patient Recruitments Patient Self-Report Pharmacology Pharmacotherapy Phospholipids Pilot Projects Placebos Polyunsaturated Fatty Acids Pregnancy Pregnancy Outcome Pregnant Women Premature Birth Premature Labor Prenatal care Public Health Randomized Reporting Research Research Personnel Risk Risk Factors Sampling Smoker Smoking Smoking Behavior Southeastern United States Sudden infant death syndrome Supplementation Tennessee Testing Tobacco Tobacco use Underserved Population United States Urine Woman adverse pregnancy outcome care outcomes cigarette smoking clinical center effective intervention effective therapy experience fatty acid supplementation fetal follow-up innovation modifiable risk neonatal death neonatal outcome nicotine craving nicotine replacement non-smoker novel strategies placebo controlled study pregnant prenatal cigarette smoking prevent primary endpoint public health priorities public health relevance recruit reduce tobacco use response retention rate secondary analysis secondary endpoint smoking cessation smoking during pregnancy success tobacco exposure tobacco use in pregnancy translational impact urinary varenicline

项目摘要

Project Summary Smoking is the most important modifiable risk factor for adverse pregnancy outcomes including preterm birth, neonatal death, and maternal complications. Smoking rates in pregnancy remain unacceptably high. Rates of smoking cessation during pregnancy are low, particularly in underserved populations, and currently approved pharmacotherapies for smoking cessation either are considered unsafe in pregnancy or have uncertain effectiveness. Identifying safe and effective interventions, which might mitigate the adverse effects of smoking on maternal-fetal outcomes, is a major public health priority. Our group has found that smokers, both pregnant and non-pregnant, have a relative deficiency in n-3 long-chain polyunsaturated fatty acids (LCPUFAs). We hypothesize that smoking-induced n-3 LCPUFA relative deficiencies may be an important mechanism contributing to tobacco-related adverse pregnancy outcomes and that n-3 LCPUFA supplementation specifically targeted to pregnant smokers may reduce these complications. Support for this hypothesis comes from a recent secondary analysis of the Omega-3 Fatty Acids Supplementation to Prevent Preterm Birth trial that found that only smokers taking n-3 LCPUFAs had a reduction in preterm labor risk as compared to non-smokers. While compelling, this study was a post hoc analysis that included only a small sample of smokers and did not collect data on smoking behaviors during follow up. Yet the ascertainment of longitudinal smoking behavior is critical, as some clinical studies have found that supplemental n-3 LCPUFAs might also reduce nicotine cravings, and lower daily cigarette use. Thus, smokers may doubly benefit from replenishing n- 3 LCPUFAs via lower risk of preterm labor and/or increased smoking cessation. To address these knowledge gaps, we are proposing a multi-center, randomized, placebo-controlled, double-blinded study of n-3 LCPUFA supplementation in 400 pregnant smokers. We will collect detailed information on smoking behavior, validated biological markers of cigarette exposure (urinary cotinine, end-expiratory carbon monoxide) and biomarkers of n-3 LCPUFA status (red blood cell phospholipid membrane fatty acids). Our specific aims of this proposal are to 1) determine the effect of supplemental n-3 LCPUFAs on gestational age at delivery and preterm labor in pregnant smokers and 2) determine the effect of n-3 LCPUFA supplementation on tobacco use in pregnant smokers. Through our recently completed pilot study, we have optimized our recruitment and retention strategies and determined the tolerability of our intervention. Our research team includes experienced researchers with prior successes in recruiting pregnant women for clinical studies and performing interventional studies for smoking cessation. We will recruit potential participants from eight obstetrics clinics across the Middle-Tennessee area. This will be the first study of supplemental n-3 LCPUFAs conducted exclusively in pregnant smokers. Our study could have a major translational impact on both adverse tobacco- related birth outcomes and smoking cessation efforts.

项目摘要吸烟是不良怀孕结果，包括早产，新生儿死亡和产妇并发症。怀孕中的吸烟率仍然令人难以置信。率怀孕期间的戒烟较低，尤其是在服务不足的人群中，目前已批准戒烟的药物治疗要么被认为是怀孕不安全的，要么不确定效力。确定安全有效的干预措施，这可能减轻吸烟的不利影响关于母亲的结果，是一个主要的公共卫生优先事项。我们的小组发现吸烟者都怀孕了和非怀孕，在N-3长链多不饱和脂肪酸（LCPUFAS）中相对缺乏。我们假设吸烟引起的N-3 LCPUFA相对缺陷可能是重要的机制促进与烟草有关的不良妊娠结局，并补充N-3 LCPUFA 专门针对孕妇吸烟者可能会减少这些并发症。支持这一假设来自对欧米茄3脂肪酸补充的最新次级分析，以防止早产出生试验发现，只有服用N-3 LCPUFA的吸烟者比较早产风险降低给非吸烟者。在引人入胜的同时，这项研究是事后分析，仅包括一小部分吸烟者，并且在随访期间没有收集有关吸烟行为的数据。然而纵向的确定吸烟行为至关重要，因为一些临床研究发现补充n-3 lcpufas也可能减少尼古丁的渴望，并减少每日香烟的使用。因此，吸烟者可能会从补充n-中获得双重受益 3 LCPUFA通过较低的早产风险和/或戒烟增加。解决这些知识差距，我们提出了一个多中心，随机，安慰剂对照，双盲的N-3 LCPUFA研究补充400名怀孕吸烟者。我们将收集有关吸烟行为的详细信息，经过验证香烟暴露的生物标志物（尿可替宁，肺碳一氧化碳）和生物标志物的生物标志物 N-3 LCPUFA状态（红细胞磷脂膜脂肪酸）。该提议的具体目的是到1）确定补充N-3 LCPUFA对胎龄的影响怀孕的吸烟者和2）确定补充N-3 LCPUFA对孕妇烟草使用的影响吸烟者。通过最近完成的试点研究，我们优化了招聘和保留率策略并确定我们干预的耐受性。我们的研究团队包括经验丰富的在招募孕妇进行临床研究和表演方面取得了成功的研究人员介入戒烟的介入研究。我们将招募八个妇产科诊所的潜在参与者跨越中间探索区。这将是对进行的补充N-3 LCPUFA进行的首次研究仅在怀孕的吸烟者中。我们的研究可能会对两种不良烟草 - 相关的出生结果和戒烟工作。